Comparison of inhaled nitric oxide and aerosolized iloprost in pulmonary hypertension in children with congenital heart surgery (original) (raw)
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Anesthesia & Analgesia, 2006
ABSTRACT Nitric oxide (NO) is a prevalent molecule in the human body responsible for many physiologic activities including pulmonary vasodilation. An exogenous, inhaled form (iNO) exists that mimics this action without directly affecting systemic blood pressure. This therapy has been implemented in the treatment of pulmonary hypertension. This review examines the efficacy of iNO in the postoperative management of infants and children with congenital heart disease. To compare the effects of postoperative iNO versus placebo and/or conventional management on infants and children with congenital heart disease. The primary outcome was mortality, while secondary outcomes included length of hospital stay, assessment of neurodevelopmental disability, number of pulmonary hypertensive crises (PHTC), changes in haemodynamics including mean pulmonary arterial pressure (MPAP), mean arterial pressure (MAP), and heart rate (HR), changes in oxygenation measured as the ratio PaO2:FiO2, and measurement of maximum methaemoglobin level as a marker of toxicity. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2004), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). We included abstracts and all languages. We included randomized and quasi-randomized controlled trials comparing iNO with placebo and conventional management, or both. Trials included only children with congenital heart disease requiring surgery and complicated by pulmonary hypertension. Data were collected on mortality, number of PHTC, changes in MPAP, MAP, HR, and PaO2:FiO2, and maximum methaemoglobin level, while data on long-term mortality, neurodevelopmental disability, and length of hospital stay were unavailable. We performed subgroup analysis by age and method of control. We performed sensitivity analysis using studies of highest methodologic quality. We included four randomized trials. We observed no differences between groups with respect to mortality (P = 0.50), PHTC (P = 0.79), change in MPAP (P = 0.16), MAP (P = 0.40), HR (P = 1.00), or PaO2:FiO2 (P = 0.46). There was a significant reduction in MPAP in the subgroup of patients from birth to three months (P = 0.005), although this finding was based on a small number of patients (N = 23). We observed no differences with the use of iNO as compared with control in the majority of outcomes reviewed. No data were available for analysis with respect to several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions because of concerns regarding methodologic quality, bias, sample size, and heterogeneity.
Pediatric Cardiology, 2014
Inhaled nitric oxide (iNO) is considered standard therapy for pediatric postcardiac surgical pulmonary hypertension (PH). Limited data suggest that inhaled iloprost (inIlo), an aerosolized prostacyclin, may be a feasible and more affordable therapeutic alternative. The goal of this study was to determine if significant hemodynamic change or adverse events would occur in postoperative congenital heart surgery (CHS) patients with PH after their transition from iNO to inIlo. This retrospective review investigated CHS patients with postoperative PH (mean pulmonary artery pressure [mPAP] [25 mmHg) between January 1, 2010 and December 31, 2011 who transitioned from iNO to inIlo. By protocol, CHS patients receiving stable doses of iNO were gradually transitioned to inIlo. After full transition, the patients received inIlo every 2 h, with a final dosing range of 1.25-5 lg/dose. Both PAP and systemic arterial pressure (SAP) were invasively measured during the transition period. Seven patients ages 10 days to 1.5 years completed the protocol. Measurements of mPAP (p = 0.27) and systolic PAP (p = 0.25) did not differ between iNO and inIlo therapy alone. No serious adverse events or complications (bleeding or thrombocytopenia) occurred. The ratio of systolic PAP to SAP decreased in all patients receiving inIlo alone (p = 0.03). Pulmonary hypertension in postoperative CHS patients can be managed successfully with inIlo, and the measured hemodynamics with this agent are similar to those observed with iNO. For the management of postoperative PH, inIlo may be a reasonable alternative, thus reducing the need for costly iNO. Larger confirmatory studies would more robustly facilitate its integration into standard care.
Circulation, 2001
Background-Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. Methods and Results-A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, nϭ10; immediately postoperative, nϭ5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48Ϯ0.38 to 0.27Ϯ0.16 (PϽ0.001). Similarly, iloprost decreased the ratio from 0.49Ϯ0.38 to 0.26Ϯ0.11 (PϽ0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6Ϯ11.9 to 34.7Ϯ21.4 nmol/L during iNO (PϽ0.01), and plasma cAMP increased from 55.7Ϯ22.9 to 65.1Ϯ21.2 nmol/L during iloprost inhalation (PϽ0.05). Conclusions-In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.
Interactive CardioVascular and Thoracic Surgery, 2015
OBJECTIVES: To investigate the effects of intravenous iloprost on pulmonary artery hypertension (PAH) in infants undergoing congenital heart surgery. METHODS: In this prospective, randomized study, the study group (n = 15) received a continuous infusion of iloprost (2.0 ng/kg/min) that was delivered immediately after weaning from cardiopulmonary bypass and continued for 72 h postoperatively. Patients in the control group (n = 12) were managed conventionally. The groups were compared in terms of postoperative data, including systolic and mean pulmonary artery (PA) pressures, PA/systemic pressure ratio, lactate level, PAH crisis, ventilation time, reintubation and lengths of intensive care unit (ICU) and hospital stay. Transthoracic echocardiography was used to assess PA pressures at 1 day, 7 days and 30 days after surgery. RESULTS: No mortality occurred. PAH crisis occurred in 2 (16.6%) patients in the control group and 4 (26.7%) patients in the study group (P = 0.53). Postoperative PA pressures and PA/systemic pressure ratios were similar between the groups (P > 0.05). The durations of ICU (P = 0.40) and hospital (P = 0.98) stays were similar between the groups. Echocardiographic studies demonstrated a significant decrease in postoperative PA pressures in the control (P = 0.001) and study (P = 0.0001) groups. However, no significant change was observed between the groups (P > 0.05). The Tukey multiple comparison test showed a significant decrease in PA pressures at each follow-up in both groups (P < 0.05). CONCLUSIONS: Intravenous iloprost demonstrated no additional benefit over the conventional management of infants with PAH after repair of intracardiac defects. Clinicians may prefer other alternative agents in infants with a high risk of PAH crisis.
The Annals of Thoracic Surgery, 1996
Postoperative pulmonary hypertension is a life-threatening, yet reversible complication of congenital heart operations. Although inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown extensively to improve short-term oxygenation and hemodynamic indices in these patients, its influence on patient outcome has not been evaluated. The purpose of this study was to assess retrospectively whether patients who fulfilled our criteria for extracorporeal life support (ECLS) for critical postoperative pulmonary hypertension still required ECLS after the administration of iNO therapy. Since January 1992, 10 patients (age 3 days to 10 months) fulfilled the criteria at our institution for ECLS for postoperative pulmonary hypertension. Of these, 5 could not be separated from cardiopulmonary bypass because of pulmonary hypertension, and 5 had critical pulmonary hypertension (pulmonary arterial pressure approaching systemic arterial pressure) causing severe cardiopulmonary compromise. Six of the 10 ECLS candidates had a sustained response to iNO and survived to discharge from the hospital, without the need for rescue ECLS. Three patients still required ECLS after 30 minutes, 4 hours, and 8 hours of beginning iNO because of failing cardiac output, and 2 survived. The remaining patient died after 5 days of iNO therapy, but was no longer a candidate for ECLS because of sepsis and multiorgan system failure. Children with critical pulmonary hypertension unresponsive to maximal conventional treatment may be managed successfully with iNO without the need for rescue ECLS. A trial of iNO should therefore be given before the use of ECLS in these patients.